Our previous studies have shown that endotoxin causes pulmonary edema by increasing pulmonary microvascular permeability and pressure (Pc). Our first objective will be to determine if reducing Pc will prevent edema after endotoxin. We will infuse E. coli endotoxin into unanesthetized sheep and prevent the rise in Pc with a vasodilator. We will estimate edema formation with the extravascular fluid/blood free dry weight ratio (EVF) and compare it to the EVF of sheep which receive endotoxin but no vasodilator. This study could lead to a better understanding of the effect of pulmonary hypertension on edema in septic patients. Pulmonary edema may also result from reduced lung lymph flow (Q-L) caused by elevated systemic venous pressure (SVP). For our second objective, we will study this by measuring Q-L and EVF in a group of sheep in which we elevate SVP. We will also elevate Pc in order to promote edema. A greater EVF and lower Q-L in the elevated SVP group compared to controls should indicate the degree to which venous pressure affects edema formation. For our final objective, we will investigate the phenomenon of proliferation of the lung lymph system when left atrial pressure is chronically elevated. We will increase left atrial pressure by 15 mmHg in sheep and measure Q-L for 2 months. Increases in Q-L over this time should allow us to evaluate the time course of lymph system proliferation and estimate its effect in preventing pulmonary edema. We will also perform morphological studies designed to determine the site of tissue fluid accumulation in these sheep. This study could help us to understand lung fluid balance in patients with chronically elevated pulmonary vascular pressures.
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